LDDRD has established an active network of collaborations aimed at structure-activity investigations and lead optimization research within selected series of novel antitumor and anti-HIV natural products. The goal is to introduce into to NCI drug development program improved members of known chemical and/or mechanistic classes currently under development and of continuing interest, as well as to introduce the best representatives of entirely new active chemical and.or mechanistic classes for consideration for entry into the drug development program. Subjects of current chemical and biological investigations include halichondrin-related compounds, e.g. halistatin, colastatins, cephalostatins, cribrostatins, spongistatins, michellamine derivatives, calonolide derivatives and related compounds, ellipticines, ellipticiniums and related agents.